2-Amino- and 2-alkylthio-4H-3,1-benzothiazin-4-ones: synthesis, interconversion and enzyme inhibitory activities

Molecules. 2009 Jan 14;14(1):378-402. doi: 10.3390/molecules14010378.

Abstract

The synthetic access to 2-sec-amino-4H-3,1-benzothiazin-4-ones 2 was explored. Compounds 2 were available from methyl 2-thioureidobenzoates 1, 2-thioureidobenzoic acids 3, and novel 2-thioureidobenzamides 6, respectively, under different conditions. 2-Alkylthio-4H-3,1-benzothiazin-4-ones 5 have been prepared from anthranilic acid following a two step route. Both, benzothiazinones 2 and 5 underwent ring cleavage reactions to produce thioureas 1 and 6, respectively. Twelve benzothiazinones were evaluated as inhibitors against a panel of eight proteases and esterases to identify one selective inhibitor of human cathepsin L, 2b, and one selective inhibitor of human leukocyte elastase, 5i.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates* / chemistry
  • Benzoates* / metabolism
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors
  • Cattle
  • Chymotrypsin / antagonists & inhibitors
  • Cysteine Endopeptidases
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Humans
  • Leukocyte Elastase / antagonists & inhibitors
  • Molecular Structure
  • Sterol Esterase / antagonists & inhibitors
  • Thiourea* / chemistry
  • Thiourea* / metabolism

Substances

  • Benzoates
  • Enzyme Inhibitors
  • Sterol Esterase
  • Cathepsins
  • Chymotrypsin
  • Leukocyte Elastase
  • Cysteine Endopeptidases
  • CTSL protein, human
  • Cathepsin L
  • Thiourea